PROJECT SUMMARY/ABSTRACT The Center of Research Excellence in Natural Products Neuroscience (CORE-NPN) at The University of Mississippi School of Pharmacy (UM), initiated ten years ago through a COBRE grant, has developed a multidisciplinary team committed to evaluating the effects of natural products on the central nervous system (CNS). The Pilot Project Program will continue in Phase III in much the same manner as in the previous two phases and will include three areas of support: 1) basic science research, which is the pipe-line for developing new data for grant applications and publications; 2) translational research, which, in conjunction with the UM Center for Clinical and Translational Science (CCTS) will facilitate the clinical evaluation of lead compounds discovered by CORE-NPN scientists; and 3) entrepreneurial research, which will allow scientists to advance their commercial discoveries with support from the UM Division of Technology management team. The Specific Aims to accomplish our goals are: Specific Aim 1: To advance the infrastructure of developmental Pilot Project Programs cultivated during Phase I and II that engage in basic, translational, and entrepreneurial research at the interface of natural products and neuroscience. This will ensure that investigators have the opportunity to obtain new data that are critical for competitive grant applications, translate their research findings to clinical studies, and to advance the commercialization of discoveries. Specific Aim 2: To enhance the rigorous assessment of the science conducted in the Pilot Project Program and promote peer-reviewed publications, presentations, and competitive grant applications. Applicants will be invited to submit a cover page and a Specific Aims page for their project which will be reviewed by the PPP Review Committee. Following this review, eight applicants will be invited to submit an R03-style proposal which will be further evaluated and proposers will present their proposals (Shark-Tank-COBRE) to the review committee, who will seek clarifications and provide guidance. Applicants will then submit a revised A-1 like proposal, addressing concerns raised which will then be forwarded to the EAC for final review and recommendation. Pending approval by the EAC, proposals will be submitted to the NIGMS for review and final approval. Outside reviewers with expertise on the subject may be invited, if necessary, for recommendations. Recipients will be required to deliver an Ignite-COBRE-Talk every quarter on their progress; additionally, recipients will be expected to present their research findings to the EAC during their annual review of our program. Specific Aim 3: To advance an infrastructure of developmental programs that include formal mentoring of investigators enrolled in the Pilot Project Program. This is the cornerstone of the success the PPP experienced in Phase I and II and will continue in Phase III. Each PPP PI will be assigned at least one mentor to help guide the young scientist's project. The mentor will be selected based on their expertise and the needs of the investigator. PPP evaluation metrics and benchmarks will be assessed and reported to the EAC biannually.